Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2007. / Härtill 4 uppsatser.

Thesis (M. S.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Lawrence Bottomley; Committee Member: Aldo Ferri; Committee Member: E. Kent Barefield; Committee Member: Levent Degertekin; Committee Member: Robert Whetten; Committee Member: Satish Kumar; Committee Member: Zhong Lin Wang.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2008. / Härtill 4 uppsatser.

The crotoxin complex protein is the major neurotoxic component in the venom of the Brazilian rattlesnake, Crotalus durissus terrificus. The purified protein can be crystallized in the form of thin platelets (less than 500 Å thick) suitable for electron crystallography and image processing techniques. The unit cell dimensions of the crystal are a = 38.8 Å, b = 38.8 Å, c = 256 Å, and α = β = γ = 90°. These crystals can grow in layers. For a three-dimensional image reconstruction this necessitates the determination of the crystal thickness in order to combine information from low dose images of crystals of the same thickness. In the past, the highest resolution image (to 3.9 Å) recorded from a crotoxin complex crystal on the electron microscope was from a crystal embedded in glucose. However, since glucose cannot be removed in order to accurately determine the crystal thickness, a different embedding technique (amorphous ice embedding) and tried. It was determined that high resolution image information (to 3.9 Å) can be recorded from crotoxin complex crystals embedded in amorphous ice. Five images of crystals preserved in amorphous ice, all exhibiting resolution to at least 9 Å, were first processed by a global averaging method from which two-dimensional projection maps were calculated. These maps were not interpretable due to variations in the images as demonstrated by a second processing method. In the second processing method the images were divided into smaller areas, or patches, and these patches were averaged. The patchwork images produced from the second process indicate that there is variation across the original images. The most likely explanation for the variation is the bending, or lack of flatness, of the crystals on the grid. The determination of mass thickness of the crystals from optical density differences between the crystals and the carbon support in images of freeze-dried crystals was explored. It was found that this method could not determine the mass thickness of crotoxin complex crystals to within one layer (64 Å), but could clearly distinguish between one and three overlapping layers of freeze-dried purple membrane which was used as a test specimen.

Structures were determined for 48 new natural products and several related compounds by NMR methods. One new natural product and two unnatural product structures were determined by X-ray diffraction. Molecular mechanics calculations on two indoles related to the neurotransmitter serotonin and on some synthetic cyclophanes were used to gain information about their preferred conformations. Considerable time is wasted redetermining the structures of known natural products when they are encountered in new sources. To help alleviate this problem, a database which searches on proton NMR chemical shifts was developed.

Thesis (MTech (Chemistry))-- Cape Peninsula University Technology, 2012 / The inclusion behaviour of a series of hydroxyl hosts with a variety of liquid guests has been investigated. The host 9-(4-methoxyphenyl)-9H-xanthen-9-ol (A1), C20H16O3, forms inclusion compounds with aniline (ANI), 3-picoline (3PIC), morpholine (MORPH), Nmethylacetamide (NMA) and N-methylformamide (NMF). Their structures have been elucidated and correlated with their thermal behaviour. The inclusion compounds A1ANI and A1MORPH were successfully solved in space group P21/c, whereas A13PIC was solved in 𝑃ī. Non-isothermal kinetics of desolvation were performed for A13PIC and A1MORPH. The packing of A13PIC and A1MORPH is characterized by (Host)(Guest) hydrogen bonds, whereas A1ANI is stabilised by (Host)(Host) hydrogen bonding. Three structures were obtained for the host A1 and the guest N-methylacetamide, with structural formulas of C20H16O3 C3H7NO (A1NMA), C20H16O3 2C3H7NO (A12NMA) and 2C20H16O3 2C3H7NO (2A12NMA). The packing of A1NMA, A12NMA and 2A12NMA are characterized by (Host)-OHO-(Guest) and (Guest)-NHO-(Guest) hydrogen bonds, which gave hydrogen bonding patterns of 𝐶2 2(7), 𝐶3 3(11) and 𝐶4 2(11) respectively. The hydrate A1NMFH2O was successfully solved in the triclinic space group 𝑃ī. The A1NMFH2O hydrogen bond pattern may be described according to Etter’s notation as 𝑅4 2(8) and 𝑅6 6(16). The host 9-(3-methoxyphenyl)-9H-xanthen-9-ol (A2), C20H16O3, forms inclusion compounds with morpholine (A2MORPH), N-methylacetamide (A2NMA) and N-methylformamide (A2NMF), with host-guest ratios 1:1. The crystal structure of the apohost was solved in Pbca with Z=8. The structures of A2MORPH and A2NMF were solved in 𝑃ī, whereas A2NMA was solved in P21/n. The packing of these structures is stabilised by (Host)(Guest) hydrogen bonds. The host 5-(4-methoxyphenyl)-5H-dibenzo[a,d]cyclohepten-5-ol (A26), C22H18O2, forms inclusion compounds with aniline (A26ANI) and morpholine (A26MORPH). A26MORPH and A26ANI crystallised in the space groups Pc and 𝑃ī respectively. The packing of these structures are characterized by (Host)-OHO-(Host) hydrogen bonding. A guest exchange reaction was performed. The host compounds 5-(4-chlorophenyl)-5H-dibenzo[a,d]cyclohepten-5-ol (C21H15OCl), 5-[3(trifluoromethyl)phenyl]-5H-dibenzo[a,d]cyclohepten-5-ol (C22H15OF3) and 5-(naphthalen-1-yl)-5H-dibenzo[a,d]cyclohepten-5-ol (C25H18O) form inclusion compounds with morpholine. All three structures were solved in 𝑃ī with the host molecules hydrogen bonded to the morpholine guests.

Novel, rationally-designed acrylate analogs of various known dipeptide substrates were found to be mechanism-based inactivators of the enzyme peptidylglycine alpha-amidating monooxygenase (PAM, EC 1.14.17.3). This enzyme is responsible for the rate-limiting and final bioactivation step, a C-terminal amidation of glycine-extended peptides, of a variety of peptide hormones including the potent pro-inflammatory compound Substance P. Protein-ligand docking studies, in tandem with in vitro kinetic analysis of these inactivators, indicated that the rational design of this class of compounds was successful in creating potent competitive inactivators of this enzyme. Pharmacological evaluation, via both acute and chronic models of inflammation in Sprague-Dawley rats, of these compounds indicates that they are highly potent anti-inflammatory agents which ameliorate both acute carrageenan-induced edema and the deleterious effects of chronic adjuvant-induced polyarthritis. Furthermore, these compounds were also able to induce a return toward a more normal phenotype in cancerous WB-Ras epithelial cells, via the interruption of the growth factor-stimulated pathway precipitated by Substance P. Finally, our modeling studies provide a structural basis for both the reaction and subsite stereospecificity of PAM toward its substrates, competitive inhibitors, and mechanism-based inactivators.

The objective of this work is to characterize and understand structure- mechanical property relationships in (meth)acrylate networks. The networks are synthesized from mono-functional (meth)acrylates with systematically varying sidegroup structure and multi-functional crosslinkers with varying mole fraction and functionality. Fundamental trends are established between the network chemical structure, crosslink density, glass transition temperature, rubbery modulus, failure strain, and toughness. The glass transition temperature of the networks ranged from -29 to 112 °C, and the rubbery modulus ranged from 2.8 to 129.5 MPa. At low crosslink density (Er < 10 MPa) network chemistry has a profound effect on network toughness. At high crosslink densities (Er > 10 MPa), network chemistry has little influence on material toughness. The characteristic ratio of the mono-functional (meth)acrylates components is unable to predict trends in thermoset toughness as a function of chemical structure, as is accomplished for thermoplastics. The cohesive energy density is a better tool for prediction of network mechanical properties. Due to superior mechanical properties, networks with phenyl ring sidegroups are further investigated to understand the effect of phenyl ring distance on toughness. This work provides a fundamental basis for designing (meth)acrylate shape memory polymer networks with specific failure strain, toughness, glass transition temperature, and rubbery modulus.

Diss. (sammanfattning) Alnarp : Sveriges lantbruksuniv. / Härtill 5 uppsatser.

Diss. (sammanfattning). Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.